[Ala12]MCD peptide: A lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors

A. Buku, B. A. Condie, J. A. Price, M. Mezei

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

An effort was made to discover mast cell degranulating (MCD) peptide analogs that bind with high affinity to mast cell receptors without triggering secretion of histamine or other mediators of the allergic reaction initiated by immunoglobulin E (IgE) after mast cell activation. Such compounds could serve as inhibitors of IgE binding to mast cell receptors. An alanine scan of MCD peptide reported previously showed that the analog [Ala12]MCD was 120-fold less potent in histamine-releasing activity and fivefold more potent in binding affinity to mast cell receptors than the parent MCD peptide. Because this analog showed marginal intrinsic activity and good binding affinity it was subsequently tested in the present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed a 50% inhibition of IgE binding to the FcεRIα mast cell receptor by using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization. Furthermore, in a β- hexosaminidase secretory assay, the peptide also showed a 50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made to relate structural changes and biologic differences between the [Ala12]MCD analog and the parent MCD peptide. The present results show that [Ala12]MCD may provide a base for designing agents to prevent IgE/FcεRIα interactions and, consequently, allergic conditions. Copyright Blackwell Munksgaard, 2005.

Original languageEnglish
Pages (from-to)132-137
Number of pages6
JournalJournal of Peptide Research
Volume66
Issue number3
DOIs
StatePublished - 1 Sep 2005

Keywords

  • FcεRIα receptor
  • Fluorescence polarization
  • Immunoglobulin E
  • Mast cell degranulating peptide
  • Rat basophilic leukemia cells
  • β-hexosaminidase

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